Age, plasma estradiol predict CNS problems in girls with precocious puberty

NEW YORK (Reuters Health) – French investigators found a central nervous system (CNS) lesion to be the cause of central precocious puberty in 100% of girls with first sign of breast development between 6 and 8 years of age and plasma estradiol levels exceeding 45 pmol/L.

As they report in the January issue of Pediatrics, Dr. Raja Brauner, of the Hopital Necker-Enfants Malades in Paris, and colleagues analyzed data on all girls with evidence of breast development before age 8 presenting at their clinic between 1982 and 2000. Included were 197 girls, among whom MRI revealed a CNS abnormality in 11. The abnormalities included six hamartomas, three gliomas, one angioma cavernosum, and one suprasellar arachnoid cyst.

The investigators note that one girl with a glioma and one with hamartoma would not have undergone MR imaging if the Lawson Wilkins Pediatric Endocrine Society (LWPES) recommendations had been followed.

In logistic regression analysis, the adjusted odds ratio for CNS abnormalities was 6.7 for age less than 6 years compared with older girls. The adjusted odds ratio was 7.7 for lack of pubic hair, and 4.1 for plasma estradiol over 110pmol/L.

To ensure 100% sensitivity in identifying girls with CNS abnormalities, the investigators recommend lowering the plasma estradiol threshold to 45 pmol/L, while age cut-off was kept at 6 years. With these criteria, no CNS abnormalities would be missed and 67 MRIs would have been avoided.

In an editorial, Dr. Paul Kaplowitz, of the Virginia Commonwealth University School of Medicine in Richmond, writes that he is troubled by the "implication that one could still justify ordering an MRI in half to two thirds of apparently healthy 6- to 8-year-olds with early puberty." Furthermore, many commercial estradiol assays are too imprecise to discriminate between subgroups of girls with central precocious puberty, he notes.

Given that the odds of finding an abnormality on MRI are about 1 in 5 in girls below age 6 with breast development, compared with 1 in 50 for those over age 6, Dr. Kaplowitz recommends simple observation for girls ages 6 to 8 with precocious puberty but no worrisome clinical findings.

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